REVIEW
The Antineutrophil Cytoplasmic
Antibody–Associated Vasculitides
Philip Seo, MD, John H. Stone, MD, MPH
Wegener’s granulomatosis, microscopic polyangiitis, and
Churg-Strauss syndrome are small- to medium-vessel vasculit-
ides linked by overlapping pathology and the presence of an-
tineutrophil cytoplasmic antibodies (ANCA). Commonly re-
ferred to as the ANCA-associated vasculitides, these diseases are
challenging to diagnose and to treat. Distinguishing the ANCA-
associated vasculitides from other forms of vasculitis or nonva-
sculitic processes (such as infection) can be particularly diffi-
cult. This review describes the clinical and pathologic hallmarks
of the ANCA-associated vasculitides, discusses the role of
ANCA assays in diagnosis and treatment, and outlines an
approach to the evaluation and management of these
diseases. Am J Med. 2004;117:39 –50. ©2004 by Elsevier Inc.
A
nticytoplasmic antibodies directed against neu-
trophils (or antineutrophil cytoplasmic anti-
bodies [ANCA]) were reported in association
with segmental necrotizing glomerulonephritis in the
early 1980s. In 1985, van der Woude and others (1) re-
ported the presence of diffuse cytoplasmic staining of
neutrophils in patients with Wegener’s granulomatosis.
In studies of patients with Wegener’s granulomatosis,
microscopic polyangiitis, or renal-limited vasculitis, Falk
and Jennette (2) noted another pattern of immunostain-
ing—perinuclear fluorescence of alcohol-fixed neutro-
phils. Today, Wegener’s granulomatosis, microscopic
polyangiitis, and the Churg-Strauss syndrome are com-
monly referred to as the ANCA-associated vasculitides.
The 1990 American College of Rheumatology classifi-
cation criteria for Wegener’s granulomatosis and the
Churg-Strauss syndrome (Table 1) (3,4) were developed
to ensure the inclusion of uniform disease populations in
research studies (5). These criteria did not address the
utility of ANCA for classification or the difference be-
tween polyarteritis nodosa and microscopic polyangiitis.
These limitations were addressed by the Chapel Hill Con-
sensus Conference (Table 2) (6). To date, widely accepted
diagnostic criteria for these diseases have not been devel-
oped.
A population-based study from Norfolk, England, re-
ported incidences of 8.5 cases per million for Wegener’s
granulomatosis, 3.6 cases per million for microscopic
polyangiitis, and 2.4 cases per million for the Churg-
Strauss syndrome (7). In two large U.S. cohorts of pa-
tients with Wegener’s granulomatosis (8,9), whites com-
prised more than 90% of all cases, whereas African
Americans, Hispanics, and Asians together represented
1% to 4% of cases. The mean age at diagnosis is about 55
years, but cases involving octogenarians are not unusual.
CLINICAL FEATURES
There is substantial overlap in many of the clinical fea-
tures of the ANCA-associated vasculitides. In some cases,
distinguishing between two or more of these diseases on
the basis of clinical features alone is difficult (Table 3).
Upper Respiratory Tract and Ears
Although patients with the Churg-Strauss syndrome or
microscopic polyangiitis may experience substantial ear,
nose, or sinus disease, this pattern of involvement is most
characteristic of Wegener’s granulomatosis. More than
90% of patients with Wegener’s granulomatosis eventu-
ally develop upper airway or ear abnormalities (8,9). The
nasal symptoms of Wegener’s granulomatosis include
nasal pain and stuffiness, rhinitis, epistaxis, and brown or
bloody crusts. Nasal inflammation may lead to septal ero-
sions, septal perforation, or, in many cases, nasal bridge
collapse—the “saddle-nose deformity” (Figure 1). Be-
cause damage to the sinuses increases susceptibility to
infections, the distinction between active Wegener’s
granulomatosis and secondary infections in the sinuses
may be challenging.
Two principal categories of ear disease— conductive
and sensorineural hearing loss—are typical of Wegener’s
granulomatosis (10–12). The most common cause of
conductive hearing loss may be Eustachian tube dysfunc-
tion due to nasopharyngeal disease. Inner ear disease in
From the Division of Rheumatology (PS, JHS), and The Johns Hopkins
Vasculitis Center (JHS), Johns Hopkins University School of Medicine,
Baltimore, Maryland.
Requests for reprints should be addressed to John H. Stone, MD,
MPH, The Johns Hopkins Vasculitis Center, 5501 Hopkins Bayview
Circle, Baltimore, Maryland 21224, or jstone@jhmi.edu.
Manuscript submitted August 18, 2003, and accepted in revised form
February 26, 2004.
© 2004 by Elsevier Inc. 0002-9343/04/$–see front matter 39
All rights reserved. doi:10.1016/j.amjmed.2004.02.030